Cancer immunotherapy refers to a therapy treating cancer using immune system in the body. Cancer cells may have cell surface molecules, e.g., proteins or carbohydrates, which may be often detected by the immune system. Cancer immunotherapy can induce the immune system to attack cancer cells by targeting these antigens. One way to activate anti-tumor immunity is to block immune checkpoint pathways. The immune checkpoint pathway refers to intracellular signaling pathways that maintain self-tolerance and protect tissues from excessive immune response that causes damage. Some immune checkpoints are primary immune evasion mechanisms for tumor cells. Therefore, inhibiting or blocking immune checkpoint may induce activation of T cells, and thus anti-tumor immune may improve.
Transforming growth factor (TGF)-β is a cytokine that regulates cell proliferation and differentiation, wound healing, extracellular matrix production, or the like. TGF-β family belongs to TGF-β superfamily, and this TGF-β superfamily includes activins, inhibins, bone morphogenetic proteins, and anti-Mullerian hormone. The tumor cells and the stromal cells within the tumors in late stages of various cancers generally overexpress TGF-β. TGF-β would lead to stimulation of angiogenesis and cell motility, suppression of the immune system, and increased interaction of tumor cells with the extracellular matrix. TGF-β receptors are serine/threonine kinase receptors, and they are divided into TGF-β receptor 1, TGF-β receptor 2, and TGF-β receptor 3. Of them, TGF-β receptor 1 is also called an activin A receptor type II-like kinase (ALK5).
Accordingly, for effective prevention or treatment of cancer, there is a need for a pharmaceutical composition capable of effectively inhibiting a TGF-β signaling pathway as well as improving antitumor immunity.